miR-24 Regulates Apoptosis by Targeting the Open Reading Frame (ORF) Region of FAF1 in Cancer Cells

BACKGROUND: microRNAs (miRNAs) are small noncoding RNAs that regulate cognate mRNAs at the post-transcriptional stage. Several studies have shown that miRNAs modulate gene expression in mammalian cells by base pairing to complementary sites in the 3'-untranslated region (3'-UTR) of the target mRNAs. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, miR-24 was found to target fas associated factor 1(FAF1) by binding to its amino acid coding sequence (CDS) region, thereby regulating apoptosis in DU-145 cells. This result supports an augmented model whereby animal miRNAs can exercise their effects through binding to the CDS region of the target mRNA. Transfection of miR-24 antisense oligonucleotide (miR-24-ASO) also induced apoptosis in HGC-27, MGC-803 and HeLa cells. CONCLUSIONS/SIGNIFICANCE: We found that miR-24 regulates apoptosis by targeting FAF1 in cancer cells. These findings suggest that miR-24 could be an effective drug target for treatment of hormone-insensitive prostate cancer or other types of cancers. Future work may further develop miR-24 for therapeutic applications in cancer biology

Hydroa vacciniforme lymphoproliferative disorder：a case report

In this study, we report a case of hydroa vacciniforme lymphoproliferative disorder (HVLPD). The patient, who was 21 years old at the time of initial consultation，suffering from recurrent papules, vesicular rashes, bleeding and black scabs on the neck, face and trunk. Serum EBV-DNA was significantly increased (2.88×107 copies/mL). The patient underwent skin biopsies twice within 2 years. The pathology of the first skin biopsy showed partial degeneration and loosening of the epidermal stratum spinosum, intraepidermal blister formation, partial epidermal detachment, and multifocal small abscesses seen in the blisters and stratum spinosum. Patchy infiltration of small lymphocytes, plasma cells, histiocytes, and eosinophils in the dermis, with no significant atypia of lymphocytes, EBER in situ hybridization was negative, which made it difficult to make a definitive diagnosis on pathology. The pathology of the second skin biopsy showed blisters visible within the patient's epidermis， and atypical lymphoid cells infiltrate around the hair follicles, sweat glands and blood vessels in the dermis. The immunohistochemical analysis indicated that lymphoid cells were positive for CD3, CD5, CD4, CD8, granzyme B and TIA-1, while CD56 and Perforin were negative, and the proliferation rate of Ki-67 was approximately 10%. EBER was positive by in situ hybridization consistent with clinicopathologic features of HVLPD. More than 1 year after receiving symptomatic treatment, the patient's rash worsened, with sometimes fever and left eyelid edema. The third skin biopsy performed in the other hospital showed that atypical lymphoid cells infiltrated the subcutaneous adipose tissue, and the proliferation rate of Ki-67 was 60%. The disease progressed to EBER-positive T-cell lymphoma. After 2 courses of chemotherapy with gemcitabine, cisplatin, dexamethasone and pegaspargase, the patient's edema subsided and the rash healed. This report demonstrates the clinical and pathologic features of the disease during its evolution and progression, with a view to enriching its diagnostic and therapeutic experience

Timing Determination of Invasive Fungal Infection Prophylaxis According to Immune Function in HSCT Patients

Patients who receive a hematopoietic stem cell transplantation (HSCT) exhibit an immune defect after recovering from neutropenia. The current guidelines do not recommend fungal prophylaxis in these patients, except for grades III to IV GVHD in HSCT. Thus, the timing for the initiation and cessation of IFI prophylaxis in immune-compromised patients remains a challenging endeavor. We retrospectively analyzed patients who received auto or allo-HSCT and monitored their immune function after recovering from neutropenia by measuring the levels of IgG, IgA, IgM, as well as the number of T, B, NK cells. We found that the level of IgG and NK cell count exhibited a significant difference with the incidence of IFI by logistic regression (p = 0.000 vs. 0.000, respectively) and conditional logistic regression (p = 0.009 vs. p = 0.002). The initiation of IFI prophylaxis was determined to be IgG < 7 mg/mL and NK cell count < 6.5 × 104/mL by an receiver operating characteristic curve separately. Tests in parallel increased the test sensitivity and specificity. Thus, the optimal timing for initiating prophylaxis in patients after HSCT could be IgG < 7 mg/mL or NK cell count < 6.5 × 104/mL. Future large-scale prospective clinical trials are required to verify these findings. Patients who are immuno-compromised after auto or allo-HSCT may benefit from a lower fungi infection incidence with immune surveillance and proper fungal prophylaxis

Three Dimensional Digital Sieving of Asphalt Mixture Based on X-ray Computed Tomography

In order to perform three-dimensional digital sieving based on X-ray computed tomography images, the definition of digital sieve size (DSS) was proposed, which was defined as the minimum length of the minimum bounding squares of all possible orthographic projections of an aggregate. The corresponding program was developed to reconstruct aggregate structure and to obtain DSS. Laboratory experiments consisting of epoxy-filled aggregate specimens were conducted to investigate the difference between mechanical sieve analysis and the digital sieving technique. It was suggested that concave surface of aggregate was the possible reason for the disparity between DSS and mechanical sieve size. A comparison between DSS and equivalent diameter was also performed. Moreover, the digital sieving technique was adopted to evaluate the gradation of stone mastic asphalt mixtures. The results showed that the closest proximity of the laboratory gradation curve was achieved by calibrated DSS, among gradation curves based on calibrated DSS, un-calibrated DSS and equivalent diameter

Experimental Study of Dowel Bar Alternatives Based on Similarity Model Test

In this study, a small-scaled accelerated loading test based on similarity theory and Accelerated Pavement Analyzer was developed to evaluate dowel bars with different materials and cross-sections. Jointed concrete specimen consisting of one dowel was designed as scaled model for the test, and each specimen was subjected to 864 thousand loading cycles. Deflections between jointed slabs were measured with dial indicators, and strains of the dowel bars were monitored with strain gauges. The load transfer efficiency, differential deflection, and dowel-concrete bearing stress for each case were calculated from these measurements. The test results indicated that the effect of the dowel modulus on load transfer efficiency can be characterized based on the similarity model test developed in the study. Moreover, round steel dowel was found to have similar performance to larger FRP dowel, and elliptical dowel can be preferentially considered in practice

Analysis of BDS-3 Real-Time Satellite Clock Offset Estimated in Global and Asia-Pacific and the Corresponding PPP Performances

The quality of satellite clock offset affects the performances of positioning, navigation and timing services, and thus it is essential to the Global Navigation Satellite System (GNSS). This research focuses on the estimation of BeiDou Navigation Satellite System (BDS) real-time precise satellite clock offset by using GNSS stations located in the Global and Asia-Pacific region based on the mixed-difference model. The precision of the estimated BDS clock corrections is then analyzed with the classification of the orbit types, satellite generations, and atomic clock types. The results show that the precision of the BDS clock offset estimated in the Asia-Pacific for Geosynchronous Earth Orbit (GEO), Inclined Geosynchronous Satellite Orbit (IGSO) and Medium Earth Orbit (MEO) satellites are 0.204 ns, 0.077 ns and 0.085 ns, respectively, as compared to those of clock offsets estimated in globally distributed stations. The average precision of the BDS-3 satellites clock offset estimated in global region is 0.074 ns, which is much better than the 0.130 ns of BDS-2. Furthermore, analyzing the characteristics of the corresponding atomic clocks can explain the performance of the estimated satellite clock offset, and the stability and accuracy of various parameters of the Passive Hydrogen Maser (PHM) atomic clocks are better than those of Rubidium (Rb) atomic clocks. In the positioning domain, the real-time clocks estimated in the global/Asia-Pacific have been applied to BDS kinematic Precise Point Positioning (PPP) in different regions. The Root Mean Square (RMS) of positioning results in global real-time kinematic PPP is within 4 cm in the horizontal direction and about 6 cm in the vertical direction. Hence, the BDS real-time clock offset can supply the centimeter-level positioning demand around the world

Mathematical model for computing precise local tie vectors for CMONOC co-located GNSS/VLBI/SLR stations

The seven co-located sites of the Crustal Movement Observation Network of China (CMONOC) in Shanghai, Wuhan, Kunming, Beijing, Xi'an, Changchun, and Urumqi are equipped with Global Navigation Satellite System (GNSS), very long baseline interferometry (VLBI), and satellite laser ranging (SLR) equipment. Co-location surveying of these sites was performed in 2012 and the accuracies of the solved tie vectors are approximately 5 mm. This paper proposes a mathematical model that handles the least squares adjustment of the 3D control network and calculates the tie vectors in one step, using all the available constraints in the adjustment. Using the new mathematical model, local tie vectors can be more precisely determined and their covariance more reasonably estimated